Summary: Core B Science The Science Core exists to provide reagents and services to the various projects within this Program Project Grant, and to the Neuropathology and Animal cores. The need for specific reagents and services are often common to multiple projects and cores. The most efficient method of operation for providing reagents and services requiring complex, expensive equipment is therefore via a central core with a highly skilled staff. For this renewal of the Program Project, the Science core will provide: i) Full length and truncated versions of the prion protein (PrP) and tau for infectivity experiments (Project 1), and structural studies including fiber diffraction (Project 2), chemical crosslinking (Project 3), and small angle X-ray scattering (Project 4). ii) Solid phase synthesis of amyloidogenic peptides including wild-type and mutant A and tau, for infectivity (Project 1) and structural (Projects 2-4) studies. iii) Anti-PrP and anti-tau antibodies will be required for biochemical characterization in Projects 1 and 2. In addition, antibodies will be needed for histopathology to be performed in Core C (Neuropathology). iv) Mass spectrometry and isotopically labeled proteins. Mass spectrometry support will be essential for analysis of proteins from cross-linking studies (Project 3), for determining protein turnover rates in vivo from mice fed isotopically labeled diet (Project 1), and for identification of A isoforms (Projects 1-4). v) The Animal core (Core D) will require screening to confirm transgenic status and genotype of animals to be used in experiments in support of Projects 1, 2, 3 and 4, which will be provided by the Science core. Leadership for the Core will be provided by Dr. Kurt Giles, an Associate Professor with over 20 years experience in neurodegenerative disease research, and by Dr Shenheng Guan, a Professor with over 20 years industrial and academic experience, who will act as co-director. Drs. Giles and Guan will be assisted by other scientists and research associates to provide the above functions.